An updated review of the existing knowledge regarding uremic toxins facilitates the design of experimental studies. We performed a literature search and found 621 articles about uremic toxicity published after a 2003 review of this topic. Eighty-seven records provided serum or blood measurements of one or more solutes in patients with CKD. These records described 32 previously known uremic toxins and 56 newly reported solutes. The articles most frequently reported concentrations of b2-microglobulin, indoxyl sulfate, homocysteine, uric acid, and parathyroid hormone. We found most solutes (59%) in only one report. Compared with previous results, more recent articles reported higher uremic concentrations of many solutes, including carboxymethyllysine, cystatin C, and parathyroid hormone. However, five solutes had uremic concentrations less than 10% of the originally reported values. Furthermore, the uremic concentrations of four solutes did not exceed their respective normal concentrations , although they had been previously described as uremic retention solutes. In summary, this review extends the classification of uremic retention solutes and their normal and uremic concentrations, and it should aid the design of experiments to study the biologic effects of these solutes in CKD.

Reviewing the current picture of uremic toxicity reveals its complexity. Focusing on cardiovascular damage as a model of uremic effects resulting in substantial morbidity and mortality, most molecules with potential to affect the function of a variety of cell types within the vascular system are difficult to remove by dialysis. Examples are the larger middle molecular weight molecules and protein-bound molecules. Recent clinical studies suggest that enhancing the removal of these compounds is beneficial for survival. Future therapeutic options are discussed, including improved removal of toxins and the search for pharmacologic strategies blocking responsible pathophysiologic pathways.

The aim of this manuscript is to initiate a constructive discussion about deviations in measured concentrations of uraemic solutes; these deviations, if not perceived or handled appropriately, may lead to incorrect interpretations of the pathophysiological role of uraemic solutes and/or to erroneous therapeutic decisions. To come to an objective approach towards this problem, variability analysis of reported concentrations may be of help. Striking outliers should either be discarded or considered together with other values which are more consistent with the majority of reported data.

Discrepancies in reported uremic toxin concentrations were evaluated for 78 retention solutes. For this analysis, 378 publications were screened. Up to eight publications per toxin were retained. The highest and the lowest reported concentrations, as well as the median reported concentration were registered. The ratio between the highest and the lowest (H/L) concentrations and, for some solutes, also the ratio between the highest and the median (H/M) concentrations were calculated. The compounds were arbitrarily subdivided into three groups based on their H/L ratio: group A, H/L < 3 (n = 33); group B, 3 < H/L < 8.5 (n = 20); and group C, H/L > 8.5 (n = 25). Solutes of groups A and B showed a low to intermediate scatter, suggesting a homogeneity of reported data. Group C showed a more substantial scatter. For at least 10 compounds of group C, extremely divergent concentrations were registered (H/M > 5.5) using scatter plot analysis. For all solutes of groups A and B, the highest reported concentration could be used as a reference. For some solutes of group C and for the compounds showing a divergent scatter analysis, however, more refined directives should be followed.

This article summarizes the current evolutions regarding artificial organs in Europe. The review emanates from the activities by four of the work groups of the European Society for Artificial Organs (ESAO) and is essentially based on the reports by these work groups at the latest ESAO meeting in Warsaw, Poland (2004). The topics are: apheresis, heart support, liver support, uremic toxins.

To make an evidence-based evaluation of the relationship between kidney failure and cardiovascular risk, we reviewed the literature obtained from a PubMed search using pre-defined keywords related to both conditions and covering 18 years (1986 until end 2003). Eighty-five publications, covering 552 258 subjects, are summarized. All but three studies support a link between kidney dysfunction and cardiovascular risk. More importantly, the association is observed very early during the evolution of renal failure: an accelerated cardiovascular risk appears at varying glomerular filtration rate (GFR) cut-off values, which were >/=60 ml/min in at least 20 studies. Many studies lacked a clear definition of cardiovascular disease and/or used a single determination of serum creatinine or GFR as an index of kidney function, which is not necessarily corresponding to well-defined chronic kidney disease. In six studies, however, chronic kidney dysfunction and cardiovascular disease were well defined and the results of these confirm the impact of kidney dysfunction. It is concluded that there is an undeniable link between kidney dysfunction and cardiovascular risk and that the presence of even subtle kidney dysfunction should be considered as one of the conditions necessitating intensive prevention of this cardiovascular risk.

The uremic syndrome is characterised by the retention of a host of compounds that in healthy subjects are secreted by the kidneys into normal urine. These compounds disturb many physiologic functions, resulting in toxicity. Many of the responsible compounds remain unknown, however, as well as many patho-physiologic actions of the known retention solutes. In this publication, we review recent new information regarding uremic toxicity. Especially difficult to remove compounds, such as protein bound and larger molecules, seem to play a role. New strategies enhancing their removal might be highly useful.

The retention in the body of compounds, which normally are secreted into the urine results in a clinical picture, called the uremic syndrome. The retention compounds responsible for the uremic syndrome are called uremic toxins. Only a few of the uremic retention solutes fully conform to a true definition of uremic toxins. Uremic patients develop atheromatotic vascular disease more frequently and earlier than the general population. The classical risk factors seem to be less important. Other factors have been suggested to be at play, and among those uremic toxins are mentioned as potential culprits. The identification, classification and characterization of the solutes responsible for vascular problems seems of utmost importance but is far from complete due to a lack of standardization and organization. The European Uremic Toxin Work Group (EUTox) has as a primary aim to discuss, analyze and offer guidelines in matters related to the identification, characterization, analytical determination and evaluation of biological activity of uremic retention solutes. The final aim remains the development of new strategies to reduce the concentration of the most active uremic solutes. These activities will at first be concentrated on reducing factors influencing cardiovascular morbidity and mortality.

The uremic syndrome is a complex mixture of organ dysfunctions, which is attributed to the retention of a myriad of compounds that under normal condition are excreted by the healthy kidneys (uremic toxins). In the area of identification and characterization of uremic toxins and in the knowledge of their pathophysiologic importance, major steps forward have been made during recent years. The present article is a review of several of these steps, especially in the area of information about the compounds that could play a role in the development of cardiovascular complications. It is written by those members of the Uremic Toxins Group, which has been created by the European Society for Artificial Organs (ESAO). Each of the 16 authors has written a state of the art in his/her major area of interest.